The goal of the project is to investigate the biological roles of members of the chemokine family of cytokines by studying chemokine actions in vivo, primarily in animal models of infectious disease. Through differential screening of a cDNA library prepared from lymphokine-activated macrophages, this laboratory discovered two mouse chemokines, Crg-2 and Mig. Crg-2 is likely the mouse homologue of the human chemokine IP-10, and the murine Mig (MuMig) was used to identify a human homologue, HuMig. Crg-2/IP-10 and Mig are relate, interferon- gamma inducible chemokines that preferentially target T lymphocytes, acting as chemotactic factors for activated T cells. Following injection of mice with interferon-gamma, mig was induced dramatically in multiple organs. In analyses of animal models infectious disease, infection of mice with the malarial parasite P. Yoellii induced mig in liver, spleen, lung and heart. Infection of mice with the protozoa T, gondii led to induction of mig early after infection in liver, lung, spleen and heart and at later times in brain. Infection of mice with vaccinia virus induced mig in liver, ovary, uterus, spleen, heart and lung. Using interferon-gamma knockout mice or anti-interferon- gamma antibodies, wee demonstrated that inductions of mig by infection with T. gondii and vaccinia virus were dependent absolutely on interferon gamma. Expression of Crg-2/PI-10 of these models was similar to that of mig, but with notable exceptions. We presume that Mig and Crg-2/IP-10 are mediating interferon-gamma dependent effects on the trafficking of activated T cells and that Mig's and Crg-2/IP-10's activities are important for host defense against a variety of pathogens. Ongoing work is concentrating on more precise localization of expression of mig and other chemokines in tissues and cells in the animal systems and on experiments to determine the biological roles for the chemokines in these systems, including the production of mice with targeted deletion of the mig gene.